Full text unavailable from EThOS. Please contact the current institution’s library for further details.

Abstract:

The aim of this thesis is to define the developmental and anatomical origins of populations of gliogenic precursor cells within accessible adult tissues such as skin and bone marrow. Skin-derived precursor cells (SKPs) are multipotent precursor cells which grow as self-renewing spheres and are capable of generating neuronal and Schwann cell progeny. However, the isolation of SKPs from skin becomes increasingly difficult throughout adult life, in particular from adult human specimens. Using a transgenic fate-mapping technique, a neural crest origin of SKPs is demonstrated. Combining this fate-mapping approach with microdissection of discrete skin regions, a highly enriched niche of SKPs is identified within the dermal papilla of the adult hair follicle. Targeted microdissection of this niche in adult human skin biopsies allows generation of similar cells from a minimal and defined volume of human tissue. Adult bone marrow-derived mesenchymal stem cells have been proposed as an alternative source of precursor cells with gliogenic potential. A similar transgenic fate-mapping approach was therefore used to identify a neural crest contribution to adult bone marrow. No evidence for a neural crest origin or gliogenic potential of bone marrow-derived mesenchymal stem cells could be found. Furthermore, transplantation of mesenchymal stem cells was associated with a failure of remyelination and adverse outcomes in focal models of demyelination. It is concluded that SKPs, rather than bone marrow-derived MSCs, represent a defined and developmentally rational source for the study and generation of glial cells from accessible adult tissues.